Background:Based on the effect of seasonal changes on human visceral function,this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippo-campal-receptor in rats,aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.Methods:Vernal equinox,summer solstice,autumn equinox,and winter solstice were selected as four experimental time points,and rats were randomly divided into normal control group,sham operation group,and pinealectomized group.The seasonal changes in corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone,hypothalamic melatonin receptor(MTR),and hippocampal corticosterone receptor(CORTR)were examined by enzyme-linked immunosorbent assay.Results:Comparing the same group between different seasons,we showed that in the normal control group,CRH,ACTH,corticosterone,and MTR were higher,while CORTR was lower in autumn and winter than in spring(all P＜.05).Compared with the normal control group,the pinealectomized group showed higher levels of corticosterone(P=.01),MTR(P=.01),and CORTR(P=.03)during spring;reduced levels of MTR and CORTR(both P＜.001)during summer;higher levels of ACTH(P=.001)and MTR(P＜.001),and lower levels of CRH(P=.001),corticosterone(P＜.001),and CORTR(P=.003)during autumn;and lower levels of CRH(P＜.001)and MTR(P=.004),and higher level of ACTH(P＜.001)in winter.Conclusions:Seasonal photoperiod acts on the pineal gland to secrete different levels of melatonin,resulting in seasonal changes in the hypothalamic-pituitary-adrenal axis-hippocampal-receptor,which may be the pathophysiological basis for the onset of seasonal affective disorder.

Background: Based on the theory of"five Zang-organs corresponding to the seasons"in traditional Chinese medicine (TCM), physiological functions including emotions vary with the seasons. We aimed to investigate the seasonal photoperiod effects of melatonin (MT) released from the pineal gland on the MT receptor (MTR)-Gs/Gi-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in the hippocampus.Methods: Rats were divided into three groups: control, operation (surgery with pineal gland removal), and pseudo-operation groups (same surgery as operation group but without removing pineal gland), and fed at specific time across the four seasons. The levels of MTR, adenylate cyclase (AC), cAMP, PKA, and CREB in the hippocampus were analyzed using ELISA. The concentrations of Gs and Gi were analyzed using Western blot. The expression of CREB mRNA was detected by PCR. Results: For intragroup comparisons, compared with spring, the levels of Gs/Gi in the control group were higher in summer, autumn, and winter (P=.009 in summer;P<.001 in autumn and winter);the levels of MTR, cAMP, PKA, and CREB in the control group were significantly higher in autumn and winter than in spring (all P<.001). The levels of MTR, cAMP, PKA, and CREB in each season were significantly lower in the operation group than in the control group (all P < .05). Significant differences were noted in Gs/Gi levels between the operation group and control group in spring, autumn, and winter (all P<.05). Conclusion: Our findings suggest that MTR-Gs/Gi-cAMP-PKA-CREB signaling pathway is involved in the seasonal photoperiod effects of the pineal gland on the hippocampus and may underpin seasonal changes in emotions. It can support the prevention and treatment of the seasonal onset of mental dis-orders, and enrich the theory of"five Zang-organs corresponding to the seasons".